VPS4A and cancer: Knockdown of ESCRT proteins, including Alix, Tsg101, Vps22, Chmp1/3, and Vps4 reduced the secretion of Hedgehog (Hh) via EVs.[127] Another mechanism involves recruitment of the ESCRT subunits TSG101 and VPS4 to the plasma membrane by adaptor protein arrestin domain‐containing protein 1 (ARRDC1), thereby promoting the generation of EVs (termed ARRDC1‐mediated microvesicles; ARMMs).[128] Apart from the ESCRT machinery, small GTPase proteins, including ARF1,[129] ARF6,[130] and RhoA,[131] also enable EVs to bud off from the plasma membrane of cancer cells.